tbuckley/cabot-search huggingface dataset:
Abstract 11900: Should Venous Thromboembolism Patients Treated With DOACs Be Dose Adjusted Like Patients With Atrial Fibrillation: Lessons From Apixaban
Authors: Lawrence Baruch, Obinna Ofoche, Olga Sherman, Persio D Lopez Loyo
Journal: Circulation (2022)

Introduction: In contrast to atrial fibrillation (AF), dose adjustment of apixaban and other DOACs is not recommended for pts with DVT or PE (VTE). Median DOAC levels were lower in VTE trials (e.g. apixaban 5-mg BID, AF 171 and 103 ng/mL vs. DVT 132 and 63 ng/mL, peak and trough, respectively), the result of a younger, lower weight population with better kidney function. Thus, VTE patients who meet or approach the apixaban dose reduction criteria may have levels far in excess of what’s needed to prevent recurrence. Hypothesis: Apixaban over exposure occurs in VTE pts at risk for elevated apixaban levels. Methods: Patients ≥ 75 yrs of age who had clinical markers that identified them as being at high risk for over exposure, including: 1) apixaban AF dose risk reduction criteria (age ≥ 80, creatinine ≥ 1.5, and wt ≤ 60-kg) and 2) approaching but not meeting dose reduction criteria (e.g. creatine 1.4, weight 65-kg) had a DOAC level measured at their anticoagulation clinic appointment. Levels were determined using liquid chromatography-mass spectrometry. Clinical decisions were made based on the “expected” apixaban levels. Results: Apixaban levels were obtained in 15 male pts. All 10 pts who were initially treated with apixaban 5-mg (2 of whom met the AF dose reduction criteria) had supratherapeutic apixaban levels on 5-mg BID. Of the 5 pts treated initially with apixaban 2.5-mg BID, 3 had adequate apixaban levels, while the other 2 had trough levels that were on the lower side. All 3 pts who met the AF dose reduction criteria (1 treated initially with 2.5-mg) had an adequate apixaban level on 2.5-mg BID. Conclusions: Apixaban treated VTE pts who meet or approach the AF dose reduction criteria are candidates for apixaban dose reduction, especially in light of the fact that peak and trough levels for VTE pts in general are lower than pts with AF.
Abstract 12333: Therapeutic Window of Low-Dose Prasugrel for Platelet Reactivity in the Chronic Phase of Post-Percutaneous Coronary Intervention: The Chaperon Study
Authors: Tatsuya Fukase, Shinichiro Doi, Dohi Tomotaka, ryota nishio, Norihito Takahashi, Yuichi Chikata, Endo Hirohisa, Hiroki Nishiyama, Iwao Okai, Hiroshi Iwata, Shinya Okazaki, Hiroyuki Daida, Tohru Minamino, Katsumi MIYAUCHI
Journal: Circulation (2022)

Introduction: There are many reports on the effects of on-treatment platelet reactivity using P2Y 12 reaction units (PRU) on the ischemic or bleeding risk in patients who underwent percutaneous coronary intervention (PCI). However, there was little report including low-dose prasugrel (2.5mg). Hypothesis: We assumed that low-dose prasugrel use may contribute to the effectiveness and safety in the chronic phase of PCI in Japanese patients. Methods: This prospective observational study included 398 patients who underwent PCI between 2017 and 2018 (mean age: 68±11 years, male: 83%). Serial PRU measurements were performed; the baseline was at 6 to 12 months after PCI, and the follow-up was after 6 months later. The PRU was measured by the VerifyNow® P2Y 12 assay, and we assessed the distribution of PRU in each P2Y 12 inhibitor, after defined PRU 86 to 238 as therapeutic window. Results: Among 398 patients, the follow-up PRU was obtained in 360 patients (90%), and 80 patients (22%) were taking prasugrel 2.5mg. The baseline PRUs of clopidogrel 75mg, prasugrel 3.75mg, and prasugrel 2.5mg were 175±64, 147±55, and 154±66, respectively ( p &lt;0.001), and the portions of PRU ≤239 (ischemic risk) were 14.6%, 4.4%, and 9.5%, respectively ( p =0.007). At the time of follow-up, a statistically significant trend of PRU was revealed in 24 patients changed clopidogrel 75mg to prasugrel 2.5mg (baseline vs. follow-up: 183±64 vs. 149±43, p =0.037). Regarding distribution of PRU, prasugrel 2.5mg was less frequent in PRU ≤85 (bleeding risk) compared to prasugrel 3.75mg (7.5% vs. 21.0%, p =0.019). In addition, a multivariable logistic regression analysis revealed that prasugrel 2.5mg use was an independent predictor of therapeutic window (odds ratio: 2.15; 95% confidence intervals: 1.01-4.59, p =0.044). Conclusions: We found prasugrel 2.5mg use after PCI significantly associated with therapeutic window. Thus, we believe low dose prasugrel use may contribute to the future risk reduction after PCI.
Abstract 12497: Pulmonary Embolism Mortality Prediction With Deep Learning Based on Computed Tomographic Pulmonary Angiography and Clinical Data
Authors: Fayez H Fayad, Zhusi Zhong, John Sollee, zhicheng jiao, Harrison Bai, Michael Atalay
Journal: Circulation (2022)

Introduction: Pulmonary embolism (PE) is a significant cause of mortality in the United States. We aimed to develop deep learning models using computed tomographic pulmonary angiography (CTPA) and clinical data to predict mortality in patients with PE. Hypothesis: Deep learning models based on CTPA and clinical data will outperform PE Severity Index (PESI) in predicting PE mortality. Methods: A total of 927 patients (163 deceased, median age 64, range 13-99, 52% female) and 3978 total CTPAs were identified via retrospective review across three institutions. Data from one institution were randomly split 7:1:2 into training, validation, and internal testing sets. Data from the two remaining institutions were used as an external testing set. Imaging features extracted from PEnet and clinical data (PESI variables) were used to train Random Survival Forest models. Performance was evaluated with concordance index (c-index) and compared to PESI predictions with the Wilcoxon signed-rank test. Kaplan-Meier analysis was performed by stratifying patients into high- and low-risk groups based on the combined imaging and clinical model prediction. Results: Models based on (a) imaging, (b) clinical, and (c) combined imaging and clinical data achieved c-index values of 0.761, 0.774, and 0.843, respectively, on the internal testing set, and 0.660, 0.713, and 0.722 on the external testing set. For both data sets, the combined model outperformed PESI (0.740 and 0.709, respectively, both p&lt;0.001). When stratifying patients into high- and low-risk groups, mortality outcomes were significantly different (p&lt;0.001, Figure). Conclusions: Deep learning models based on combined CTPA features and clinical data outperform PESI for mortality prediction in PE. The addition of imaging to clinical features improves performance compared to clinical features alone.
Abstract 12249: Optimal Timing of Extracorporeal Membrane Oxygenation (ECMO) Application for the Prognosis of Patients With Acute Coronary Syndrome (ACS) Accompanying Cardiogenic Shock
Authors: Dong-Gil Kim, Sung Uk Kwon
Journal: Circulation (2022)

Introduction: Advances in mechanical circulatory support (MCS) devices and several studies showing that early application of MCS devices can improve survival rates in cardogenic shock (CS) patients are increasing interest in the usefulness of MCS devices in CS patients. However, studies on the optimal use and timing of application of MCS device in CS patients are still lacking. Methods: The RESCUE study is multicenter, retrospective, and prospective registry of patients that presented with CS. From January 2014 to December 2018, 1247 patients with CS were enrolled from 12 major centers in Korea. Among enrolled patients, ECMO was applied to 238 of 693 patients who performed percutaneous coronary intervention (PCI) with acute coronary syndrome. The primary endpoint was a composite of in-hospital, 30-day, 6-month and 12-month mortality according to ECMO application timing. Results: There was no difference in the 30-day mortality in ACS patients with CS according to ECMO application timing before and after PCI. However, when stratified by time from CS recognition to ECMO application (Shock to ECMO application time, ≤100 minute vs. &gt;100 minute), 30-day Kaplan-Meier survival curve showed differences according to ECMO application timing. When the time from CS to ECMO application less than 100 minutes, patients who applied ECMO during or after PCI had a 34% reduction in 30-mortality compared to patients who applied ECMO before PCI (HR = 0.64, 95% CI: 0.39-1.03; P = 0.07). And, when the time from CS to ECMO application exceeded 100 minute, patients who applied ECMO during or after PCI had an approximately twice the 30-day mortality compared to patients who applied ECMO before PCI (HR = 2.03, 95% CI: 1.07-3.85; P = 0.03). Conclusions: According to ECMO application timing, prognosis of ACS patients with cardiogenic shock was different. In case of exceed 100 minute, early initiation of ECMO application was associated with improved prognosis in 30-day mortality.
Abstract 12498: Incidence Of Non-Sustained Ventricular Tachycardia and Arrhythmic Disease Progression During Follow-Up in Hypertrophic Cardiomyopathy Patients
Authors: Louise Bjerregaard, Christoffer H Nielsen, Steen H Poulsen, Morten S Jensen
Journal: Circulation (2022)

Introduction: One of the most well-established risk markers for sudden cardiac death is non-sustained ventricular tachycardia (NSVT; 3 ventricular beats with a rate of ≥120 bpm, lasting for &lt;30 seconds). Forty-eight-hours Holter monitoring is recommended to identify NSVT in patients with hypertrophic cardiomyopathy (HCM) . Purpose: The study aims to estimate the 48 hour-incidence of NSVT in HCM patients and to analyze arrhythmic disease progression during follow up. Methods: The study retrospectively evaluated HCM patients enrolled in the Registry for Hereditary Cardiovascular Diseases from 2011 to 2020. A total of 145 patients met the inclusions criteria to be a proband with HCM or a relative with left ventricular hypertrophy ≥13mm. A cross sectional analysis was done in 131 patients with at least one available Holter monitoring. A follow-up Holter monitoring was available in 97 patients. Results: Of 145 patients, the mean age was 54±15 years and 98 (68%) were male. The proportion of patients free of NSVT were 66% after 48 hours of Holter monitoring (n=131) (Kaplan-Meier estimates). Fifteen percent of NSVTs occurred from 36 to 48 hours into the Holter monitoring. The mean follow-up time between first and latest Holter (n=97) was 4.3 (±2.5) years and the median Holter monitoring time was both 48 (IQR, 48-48) hours at the first and 48 (IQR, 47-48) hours at the latest Holter. The proportion of patients free of NSVT in the first 48 hour Holter monitoring was 69% compared to 63% in the latest 48 hour Holter monitoring (p=0.17). Wilcoxon signed rank test showed no difference in number of ventricular cycles or the calculated frequency analyzing the first episode of NSVT in each Holter. Cox regressions analysis showed no significant difference in event rates between first and latest Holter (HR 0.84, 95% CI 0.26-2.70, p=0.77) and no association between age and NSVT (HR 1.03, 95% CI 0.83-1.28, p=0.80). Conclusions: NSVT occurred with an incidence rate of 34% per 48-hours Holter monitoring. An important part of NSVTs was identified in the last 12 hours of monitoring. The was no significant progression in the incidence rate of NSVT nor the characteristics of NSVT during follow up. Age had no effect on the incidence of NSVT.
Abstract 12152: Recurrent Cerebrovascular Accidents Following Myocardial Infarction With Mechanical Rupture
Authors: Jonathan Stewart, Sumon Roy, Cory R TRANKLE, Vigneshwar KASIRAJAN, Rahul Rajeev
Journal: Circulation (2022)

Background: Mechanical complications of myocardial infarction (MI), including ventriculoseptal ruptures (VSR) and pseudoaneurysms, are potentially life-threatening events but are less common in the era of timely primary percutaneous coronary interventions. Rare case reports describe MI complicated by VSR requiring repair, with delayed left ventricular (LV) pseudoaneurysm formation from the site of VSR repair. We present an atypical manifestation of one such case. Case Presentation: A 55-year-old male was admitted with late presentation inferior MI complicated by inferior VSR, requiring extracorporeal membrane oxygenation and surgical repair. Five months later, he was admitted with left upper extremity weakness and sensory loss. Brain imaging revealed an acute infarct of the precentral gyrus and subacute punctate infarcts of the centrum ovale. He was referred for cardiac magnetic resonance imaging, which revealed a large 6.8x4.9 cm inferior LV pseudoaneurysm containing a large thrombus (Figure 1). He underwent urgent surgery revealing a left ventricular inferior wall defect (Figure 2) and pseudoaneurysm with large mural thrombus. The pseudoaneurysm was successfully repaired via Dacron patch placement and thrombus evacuated. Conclusion: Although less common in the modern era, mechanical complications are possible after severe MI. Clinicians should be aware of the potential for atypical manifestations of these complications, including cardioembolic events that can arise within large pseudoaneurysms.
Abstract 12563: Creation of an Artificial Intelligence Model For Prediction of Major Adverse Cardiovascular Events Late After Tetralogy of Fallot Repair
Authors: Ayako Ishikita, Chris McIntosh, Myunghyun M Lee, Stavroula Raptis, Tiffany Liang, Kate A Hanneman, Gauri Karur, Susan L Roche, David Barron, Edward Hickey, Rachel M Wald
Journal: Circulation (2022)

Introduction and Hypothesis: Despite successful tetralogy of Fallot repair (rTOF) in childhood, advancing age is associated with escalating risk of morbidity and mortality. Published risk scores for prediction of major adverse cardiovascular events (MACE) typically incorporate invasive and/or specialized measures. We hypothesized that an artificial intelligence (AI) model using an array of parameters available in routine clinical practice could successfully predict MACE in rTOF. Methods: Adults with rTOF were identified using institutional databases (the prospective observational Comprehensive Outcomes Registry Late After Tetralogy of Fallot Repair [CORRELATE] and the retrospective Toronto Outcomes Registry of Congenital Heart disease [TORCH]). A random forest AI model for prediction of MACE was trained on CORRELATE using repeated random sub-sampling validation. External validation was achieved using non-overlapping retrospective data from TORCH. The MACE composite outcome included all-cause mortality, resuscitated sudden death, sustained ventricular tachycardia (&gt;30 seconds) or heart failure (hospital admission&gt;24 hours). Results: In total, 804 subjects were studied and MACE was observed in 73 (9%) subjects. Patients were either included in the training dataset (n=312, 59% male, median age 32 years [IQR 23-43], median follow-up 6 years [IQR 4-7]) or the testing dataset (n=492, 58% male, median age 26 years [IQR 20-37], median follow up 10 years [IQR 6-10]). Variables incorporated into the AI model are shown (Figure 1). Predictive capacity of the AI models were similar in testing (AUC 0.81, CI 0.75-0.86) and training (AUC 0.88, CI 0.71-0.99) datasets with excellent receiver operating characteristics (Figure 1). Conclusions: An AI model based on routinely used and widely available clinical and imaging variables could successfully predict MACE in rTOF. Further study is required to determine the value of AI for risk management in rTOF.
Abstract 11205: Pharmacological and Non-Pharmacological Parasympathomimetic Interventions Prevent Trastuzumab-Induced Cardiotoxicity Through Attenuating Impaired Mitochondrial Function
Authors: Thawatchai Khuanjing, Chayodom Maneechote, Benjamin Ongnok, Nanthip Prathumsap, Apiwan Arinno, Titikorn Chunchai, Busarin Arunsak, Siriporn Chattipakorn, Nipon Chattipakorn
Journal: Circulation (2022)

Introduction: Although the use of trastuzumab (Trz) has effectively reduced the mortality rate in breast cancer patients, Trz-induced cardiotoxicity (TIC) has become a serious complication. Parasympathetic activations via either electrical vagus nerve stimulation (VNS) device or acetylcholinesterase inhibitor donepezil (DPZ), have been shown to exert cardioprotection in various heart diseases. However, the cardioprotective effects of VNS and DPZ on left ventricular (LV) function, autonomic function, and mitochondrial function in TIC rats are unknown. Hypothesis: Both VNS and DPZ protect the heart against TIC by reducing LV dysfunction, sympathovagal imbalance, and mitochondrial dysfunction. A combination of VNS and DPZ treatment exerts a better benefit than either single intervention. Methods: Adult male Wistar rats (N=25) were subjected to VNS device implantation. Then, rats were assigned into five groups (N=5/group), including (i) control without VNS (C), (ii) Trz (4 mg/kg/day, I.P., 7 days), (iii) Trz+DPZ (5 mg/kg/day, P.O., 7 days) (TrzD), (iv) Trz with VNS (TrzV), and (v) Trz+DPZ with VNS (TrzVD). LV function and heart rate variability (HRV) were performed. All hearts were collected to determine mitochondrial reactive oxygen species (ROS) levels and mitochondrial morphology. Results: Trz rats had a reduced LV ejection fraction, impaired HRV as shown by increased LF/HF ratio, and mitochondrial dysfunction shown by increased ROS levels and dysmorphology (Figures 1A-D). Treatment with either DPZ, VNS, or the combined treatment exerted similar cardioprotection via reducing sympathovagal imbalance and mitochondrial injury, leading to improved LV function, (Figures 1A-D). Conclusions: Promoting parasympathetic activity using VNS, DPZ, or the combined treatment similarly protected the heart against TIC via improving HRV, mitochondrial function, and mitochondrial morphology, suggesting a novel potential strategy for patients receiving Trz.
Abstract 11571: Associations of Adipokine Levels With Levels of Remnant Cholesterol: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Renato Quispe, Ty Sweeney, Chiadi E Ndumele, Seth S Martin, Steven R Jones, Matthew A Allison, Matthew Budoff, Mohamed B Elshazly, Erin D Michos
Journal: Circulation (2022)

Introduction: The metabolic phenotype of obesity is characterized by high levels of triglyceride (TG)-rich lipoproteins and remnant particles, which are atherogenic. Adipokines are endogenous hormones released from adipose tissue with several metabolic effects. We aimed to assess the association between adipokines and levels of remnant cholesterol (RC). Methods: We studied 1,791 MESA participants of an ancillary study who had adipokine levels measured (leptin, adiponectin, resistin) and CT assessment of visceral and subcutaneous adipose tissue at either visit 2 or 3. RC was calculated as non-HDL-C minus LDL-C, measured at the same visit as the adipokines. Multivariable adjusted linear regression models were used to assess the cross-sectional association between adipokines and RC levels. Results: Mean ± SD age was 64.5 ± 9.6 years; 52% women, 40% White, 21% Black, 26% Hispanic, and 14% Chinese-American participants. Median (IQR) of leptin, resistin and adiponectin were 13.1 (5.6-28.2) ng/mL, 14.9 (11.9-18.8) ng/mL and 17.5 (11.9-26.4) ng/mL, respectively. Those in the highest tertile of adiponectin had lower levels of TG [89 mg/dL (65-136)] and RC [18.8 mg/dL (15-24.9)] compared to the lowest tertile [TG 130 mg/dL (93-180); RC 23.6 mg/dL (19.1-30.2), p&lt;0.01]. Individuals in the highest tertile of leptin had higher levels of TG [121 mg/dL (83-177)] and RC [22.8 mg/dL (17.8-30)] compared to the lowest tertile [TG 100 mg/dL (69-141); RC 20 mg/dL (15.7-25.4), p&lt;0.01]. Diabetes was more prevalent in lowest tertile of adiponectin (18.8% vs. 9.1%) and highest tertile of leptin (15.8% vs. 10.7%) compared to their lowest tertiles. No significant differences were seen across resistin tertiles. After adjustment, levels of adiponectin and leptin remained significantly associated with higher levels of RC (Table) . Conclusion: Lower adiponectin and higher leptin levels were associated with worse metabolic profile, and independently associated with higher levels of RC.
Abstract 11403: Systemic Administration of High Mobility Group Box 1 Fragment Improves Cardiac Functions via Activating Tissue Healing Pathway of Bone-Marrow Mesenchymal Stem Cell in a Porcine Ischemic Cardiomyopathy Model
Authors: Yoshito Ito, Masashi Kawamura, Takuji Kawamura, Katsuto Tamai, Daisuke Yoshioka, Tetsuya Saito, Ryohei Matsuura, Yusuke Misumi, Akima Harada, Takasumi Goto, Tadashi Watabe, Atsushi Yamada, Masaki Taira, Kazuo Shimamura, Koichi Toda, Shigeru Miyagawa
Journal: Circulation (2022)

Introduction : Regenerative therapy for heart failure (HF) points to bone marrow mesenchymal stem cell (BM-MSC) as a promising cell source. High mobility group box 1 (HMGB1) is a nuclear protein involved in tissue homeostasis. In this study, we developed an HMGB1 fragment containing a BM-MSC mobilization domain. Hypothesis: We hypothesize that the HMGB1 fragment improves cardiac function by activating a tissue healing pathway of BM-MSC within a porcine ischemic cardiomyopathy (ICM) model as a pre-clinical study. Methods: Gottingen mini pigs weighing 15-25 kg were used. An ICM model was generated by placing an ameroid constrictor ring (internal diameter; 3.5 mm) on the left anterior descending artery (LAD). After 4 weeks, either the HMGB1 fragment (HMGB1 group; 3 mg/kg, n=6) or normal saline (control group; n=5) was administered intravenously with one dose every 48 h for five times. We examined cardiac function before and 8 weeks post treatment through echocardiography, cardiac magnetic resonance imaging (cMRI) with late gadolinium enhancement (LGE), and a fluoroscopy-guided pressure wire study. Then, histological analysis was performed. Results: In echocardiography, ejection fraction significantly improved in the HMGB1 group compared with the control (+11.1% vs -4.8%, p=0.0003). cMRI with LGE demonstrated that the areas of damaged myocardium (core infarct zone + border zone) in the LAD region was reduced in the HMGB1 group compared with the control group (-11.9% vs +17.9%, p=0.0090). Coronary flow reserve (CFR) and resistive reserve ratio (RRR) were evaluated through pressure wire study; they improved in the HMGB1 group compared with the control group (ΔCFR; +0.38 vs +0.01, p=0.0249, ΔRRR; +0.42 vs +0.07, p=0.0275). Histological analysis showed that cardiomyocyte size (26.6 μm vs 38.0 μm, p=0.0339) and areas of fibrosis were smaller (9.8% vs 11.6%, p=0.1649), and the density of CD31-positive endothelial cells was higher (1033/mm 2 vs 640/mm 2 , p=0.0339) in the HMGB1 group than in the control group. Conclusions: Systemic administration of the HMGB1 fragment improved cardiac function, coronary flow reserve, and reduced cardiac fibrosis in an ICM model. This drug-induced activation of inner tissue repair and regeneration is a novel approach to treat HF.